A serological mass survey was carried out in Wuzhou City in 1980, 1,136 IgA/VCA-positive persons being followed up for 4 years. Altogether 35 NPC cases were detected, of which 15 (43%) were in stage I and 17 (48.5%) in stage II, early cases (I + II) thus amounting to 91.5%. The detection rate of early cases was 2.9 times higher than in our outpatient clinic. IgA/VCA antibody could be detected 16-41 months prior to clinical diagnosis of NPC. We conclude that, if IgA/VCA-positive individuals are examined routinely once a year, NPC can be detected in the early stages of evolution. The annual detection rate of NPC in IgA/VCA antibody-positive individuals was 31.7 times higher than that of the annual incidence of NPC in the general population in the same age group, while during the 4-year follow-up period the incidence was 7.5 times higher than in the general population for the same age group. These results further indicate that EB virus plays an important role in the development of NPC, and that serological screening and follow-up studies are valuable for the early detection of NPC.
These findings indicated that shRNA could suppress HBV expression and replication for genotypes A, B, and C, promising an advance in treatment of HBV. However, the emergence of resistant mutants in HBV quasispecies should be considered.
Objective
Patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) have a high frequency of venous thromboembolic events and a hypercoagulable state. As C5a‐primed neutrophils play an important role in the development of AAV, we investigated whether C5a‐induced neutrophil tissue factor (TF)–expressing microparticles (MPs) and neutrophil extracellular traps (NETs) might promote hypercoagulability in AAV.
Methods
TF‐expressing MPs were measured by flow cytometry. TF‐expressing NETs were assessed by confocal microscopy. Levels of thrombin–antithrombin complexes were determined by enzyme‐linked immunosorbent assay. The effect of C5a in sera from AAV patients was evaluated by treating neutrophils with C5a receptor antagonist before incubation with sera from AAV patients with active disease.
Results
Treatment of C5a‐primed neutrophils with antineutrophil cytoplasmic antibody (ANCA)–positive IgG resulted in the release of TF‐bearing MPs and NETs. Neutrophils from healthy donors treated with sera from patients with active AAV released TF‐bearing MPs and NETs, which were abolished by treatment with C5a receptor antagonist. Involvement of TF in MP‐ or NET‐dependent thrombin generation was indicated by the findings of antibody neutralization studies. NETs with thrombin‐generating capacity were demonstrated by DNase I treatment.
Conclusion
C5a‐primed neutrophils produce TF‐expressing MPs and NETs after stimulation with ANCAs, indicating a mechanism for hypercoagulability in AAV that was not previously recognized.
Three pathogenic human coronaviruses have emerged, with SARS-CoV-2 causing a global pandemic. While therapeutic antibodies targeting the SARS-2 spike currently focus on the poorly conserved receptor-binding domain, targeting essential neutralizing epitopes on the more conserved S2 domain may provide broader protection. We report three antibodies, binding epitopes conserved on the pre-fusion MERS, SARS-1 and SARS-2 spike S2 domains. Antibody 3A3 binds a conformational epitope with ~2.5 nM affinity and neutralizes in in vitro SARS-2 cell fusion and pseudovirus assays. Hydrogen-deuterium exchange mass spectrometry identified residues 980-1006 in the flexible hinge region at the S2 apex as the 3A3 epitope, consistent with binding to natural and engineered spike variants. This location at the spike trimer interface suggests 3A3 prevents the S2 conformational rearrangements required for virus-host cell fusion. This work defines a highly conserved vulnerable site on the SARS-2 S2 domain and may help guide the design of pan-protective spike immunogens.TEASERA conserved, neutralizing epitope in the S2 domain of coronavirus spike was identified as a target for pan-coronavirus therapy and vaccination.
Two nasopharyngeal carcinoma (NPC) cell lines and one keratinocyte cell line could be infected with Epstein-Barr virus (EBV) by cocultivation with virus-producing cells but not by cell-free virus. Using porous culture inserts to manipulate the cell-to-cell contact, we demonstrated that contact between EBV donor B cells and EBV recipient epithelial cells was required for the infection. Cell-to-cell contact not only provided a CR2-independent route of infection but also enhanced CR2-mediated infection in a synergistic manner. Activity of two EBV promoters (Cp and Wp) and expression of EBNA2 were detected in the infected population. A small proportion of the infected cells spontaneously entered an EBV lytic state, which could be induced prominently by chemical treatment. This study provides information on how EBV may infect epithelial cells in vivo, such as at the onset of NPC development.
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